We propose to continue the development of new liquid chromatograph-mass spectrometer systems which permit direct and continuous monitoring of samples eluting from the chromatograph and which can be applied to biological molecules of extremely low volatility. The LC-MS interface developed in this project employs laser vaporization and molecular beam techniques to achieve rapid vaporization, efficient sample transport, and minimal contamination of the mass spectrometer. In the continuation of this work we propose to establish the utility of the crossed-beam LC-MS for genuine biomedical problems, to develop second-generation LC-MS systems toward both improving the performance and decreasing the cost and complexity. Also, a new approach to a relatively inexpensive, universal LC detector is proposed.